2024
In vivo AAV–SB-CRISPR screens of tumor-infiltrating primary NK cells identify genetic checkpoints of CAR-NK therapy
Peng L, Renauer P, Sferruzza G, Yang L, Zou Y, Fang Z, Park J, Chow R, Zhang Y, Lin Q, Bai M, Sanchez A, Zhang Y, Lam S, Ye L, Chen S. In vivo AAV–SB-CRISPR screens of tumor-infiltrating primary NK cells identify genetic checkpoints of CAR-NK therapy. Nature Biotechnology 2024, 43: 752-761. PMID: 38918616, PMCID: PMC11668911, DOI: 10.1038/s41587-024-02282-4.Peer-Reviewed Original ResearchPrimary NK cellsTumor-infiltrating NKCAR-NK cellsNK cellsGenetic checkpointsNatural killerChimeric antigen receptor (CAR)-NK cellsHuman primary NK cellsSolid tumor mouse modelNK cell-based immunotherapyIn vivo antitumor efficacyCAR-NK therapyNK cell therapyCell-based immunotherapyNK cell functionTumor mouse modelTumor infiltrationAntitumor efficacyCell therapyCytokine productionEnhanced cytotoxicityMouse modelSingle-cell transcriptomic landscapeClinical potentialCell function
2022
Genome Engineering for Next-Generation Cellular Immunotherapies
Park JJ, Lee KAV, Lam SZ, Tang K, Chen S. Genome Engineering for Next-Generation Cellular Immunotherapies. Biochemistry 2022, 62: 3455-3464. PMID: 35930700, PMCID: PMC11320893, DOI: 10.1021/acs.biochem.2c00340.Peer-Reviewed Original ResearchConceptsGenome engineeringCellular immunotherapySynthetic biology approachesKnockout of genesGenome engineering approachesGenetic screening approachCell therapyNK cell therapyCAR-NK cellsBiology approachHost-graft interactionsNovel target discoveryLong-term persistenceImmune cell typesCRISPR-CasFuture therapeutic developmentTarget discoveryGenetic modificationCell typesAllogeneic contextTumor effect
2020
Phase I Trial of Expanded, Activated Autologous NK-cell Infusions with Trastuzumab in Patients with HER2-positive Cancers
Lee S, Shimasaki N, Lim J, Wong A, Yadav K, Yong W, Tan L, Koh L, Poon M, Tan S, Ow S, Bharwani L, Yap Y, Foo M, Coustan-Smith E, Sundar R, Tan L, Chong W, Kumarakulasinghe N, Lieow J, Koe P, Goh B, Campana D. Phase I Trial of Expanded, Activated Autologous NK-cell Infusions with Trastuzumab in Patients with HER2-positive Cancers. Clinical Cancer Research 2020, 26: 4494-4502. PMID: 32522887, DOI: 10.1158/1078-0432.ccr-20-0768.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBiopsyBreast NeoplasmsCoculture TechniquesCombined Modality TherapyDose-Response Relationship, DrugFemaleHumansImmunotherapyK562 CellsKiller Cells, NaturalMaleMiddle AgedReceptor, ErbB-2Response Evaluation Criteria in Solid TumorsStomach NeoplasmsTransplantation, AutologousTrastuzumabConceptsAntibody-dependent cell cytotoxicityAutologous NK cellsNK cellsPhase I trialI trialNK cells expressed high levelsNatural killer (NK) cellsActivated autologous NK cellsHER2-positive solid tumorsPhase I dose escalationPeripheral blood NK cellsHER2-positive malignanciesNK cell infusionNK cell therapyBlood NK cellsNK cell expansionIncreased NK cellsPhase II trialPreliminary antitumor activityNK cell activityCells expressing high levelsHER2-positive cancersStable diseasePartial responseII trial
2018
Immunotherapy in acute myeloid leukemia and myelodysplastic syndromes: The dawn of a new era?
Liu Y, Bewersdorf JP, Stahl M, Zeidan AM. Immunotherapy in acute myeloid leukemia and myelodysplastic syndromes: The dawn of a new era? Blood Reviews 2018, 34: 67-83. PMID: 30553527, DOI: 10.1016/j.blre.2018.12.001.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHematopoietic stem cell transplantAcute myeloid leukemiaImmune checkpoint inhibitorsMyelodysplastic syndromeCheckpoint inhibitorsCell-based therapiesMyeloid leukemiaAllogeneic hematopoietic stem cell transplantCytotoxic T-lymphocyte-associated protein 4T-lymphocyte-associated protein 4Cell death protein 1Cell-based vaccinesNK cell therapyApplication of immunotherapyDeath protein 1Stem cell transplantAntibody-targeted therapyChimeric antigen receptorAntibody-based therapiesGemtuzumab ozogamicinDendritic cellsCell transplantImmunotherapeutic drugsT cellsClinical development
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